Editors' ChoicePeriodontitis

DELivering new therapies for chronic inflammation

Sci. Signal.  06 Oct 2015:
Vol. 8, Issue 397, pp. ec286
DOI: 10.1126/scisignal.aad5682

A chronic inflammatory condition called periodontitis is prevalent in nearly half of adult teeth and gums in the U.S. population. Periodontitis can increase a patient’s risk of developing other inflammatory diseases in the heart (atherosclerosis) and joints (rheumatoid arthritis). Shin et al. capitalized on the natural anti-inflammatory activity of the protein DEL-1, finding that it not only blocked excessive immune cell infiltration into the periodontium but also had inhibited osteoclastogenesis, thereby reducing bone loss by interrupting the signaling pathways to osteoclasts, which are bone-resorbing cells. In vitro, in human and mouse osteoclast precursor cells, DEL-1 prevented osteoclast differentiation by inhibiting the activity of the transcription factor NFATc1. In vivo, in mouse and nonhuman primate models of periodontitis, giving DEL-1 locally reduced inflammation and tissue destruction. The mechanism appeared two-pronged: DEL-1 worked “upstream” in disease-associated signaling pathways to prevent inflammatory cell recruitment to the teeth and gums and acted “downstream” to stop osteoclastogenesis. On the basis of the data from a monkey model that closely represents the human disease, anatomy, and immune system, DEL-1–based therapeutics could rapidly translate into clinical use.

J. Shin, T. Maekawa, T. Abe, E. Hajishengallis, K. Hosur, K. Pyaram, I. Mitroulis, T. Chavakis, G. Hajishengallis, DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates. Sci. Transl. Med. 7, 307ra155 (2015). [Abstract]